This application seeks to study HIV infection in primary macrophages specifically to study the sites in the LTR which control replication in these cells. The hypotheses to be tested are that NF-kB binding sites are likely to be important for HIV expression in macrophages and that other macrophage-specific factors are likely to be involved. The PI will accomplish this first by mutagenesis of the NF-kB and other sites within the HIV LTR. In the Second Aim, the PI will determine the influence of the macrophage activation using the mutated infectious clones. In Specific Aim 3, the PI will examine synergy between the NF-kB sites and macrophage activation. The approach is to substitute other macrophage- specific transcription factor motifs for HIV-enhancer sequences and then examine the effect on viral replication. The PI hopes to find novel sites in the LTR that affect virus replication in macrophages.